» Articles » PMID: 36006930

Mutations in the TERC Template Sequence Can Be Incorporated into the Telomeres of Human Tumors

Overview
Journal PLoS One
Date 2022 Aug 25
PMID 36006930
Authors
Affiliations
Soon will be listed here.
Abstract

Telomerase-mediated lengthening is a mechanism by which some cancer cells avoid senescence-mediated cell cycle arrest due to shortened telomeres. By reverse transcribing an RNA template, encoded by TERC, the enzyme telomerase synthesizes the elongation of telomeric DNA using the 3' end of the chromosome as a primer. TERC harbors a highly conserved template region consisting of 11 nucleotides spanning hg19 coordinates chr3:169482793-169482803. In human cell lines, when TERC was mutated to alter its template region, telomerase generated the predicted mutant telomeric repeats. However, it is unknown if this can occur in human clinical samples. Here, we report on the rare occurrence of two tumor samples where TERC template mutations were reflected in telomeric repeats.

Citing Articles

A persistent variant telomere sequence in a human pedigree.

Hinchie A, Sanford S, Loughridge K, Sutton R, Parikh A, Gil Silva A Nat Commun. 2024; 15(1):4681.

PMID: 38824190 PMC: 11144197. DOI: 10.1038/s41467-024-49072-9.

References
1.
Lin J, Smith D, Blackburn E . Mutant telomere sequences lead to impaired chromosome separation and a unique checkpoint response. Mol Biol Cell. 2004; 15(4):1623-34. PMC: 379261. DOI: 10.1091/mbc.e03-10-0740. View

2.
Frampton G, Fichtenholtz A, Otto G, Wang K, Downing S, He J . Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol. 2013; 31(11):1023-31. PMC: 5710001. DOI: 10.1038/nbt.2696. View

3.
Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

4.
Kim N, Piatyszek M, Prowse K, Harley C, WEST M, Ho P . Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 266(5193):2011-5. DOI: 10.1126/science.7605428. View

5.
Sharaf R, Montesion M, Hopkins J, Song J, Frampton G, Albacker L . A pan-cancer landscape of telomeric content shows that RAD21 and HGF alterations are associated with longer telomeres. Genome Med. 2022; 14(1):25. PMC: 8883689. DOI: 10.1186/s13073-022-01029-7. View